2-phenyl-3-amido-5,6-dimethoxyindoles



United States Patent 3,467,670 2-PHENYL-3-AMIDO-5,6-DIMETHOXYINDOLESJohn T. Suh, Mequon, Wis., assignor to McNeil Laboratories,Incorporated, a corporation of Pennsylvania No Drawing. Originalapplication Oct. 5, 1964, Ser. No. 401,712, now Patent No. 3,370,063,dated Feb. 20, 1968. Divided and this application Apr. 28, 1967, Ser.

Int. Cl. C07d 27/56 US. Cl. 260-32614 4 Claims ABSTRACT OF THEDISCLOSURE The compounds are of the class of 2-phenyl(orcycloalkyl)-3-amido-5,6-dimethoxyindoles, useful as ultraviolet lightabsorbers.

CH30 R3 In the above formula R stands for hydrogen, loweralkylcarbonyl,cyano-loweralkyl or loweralkyl-carbonylaminoloweralkyl; R stands foraryl such as phenyl or naphthyl, substituted phenyl such as halophenyl,alkylphenyl, cyanophenyl, carboxyphenyl, aminophenyl,loweralkylaminophenyl, di-loweralkylaminophenyl, halomethylphenyl,loweralkylamino, amino-loweralkyl andloweralkyl-carbonylamino-loweralkyloxyphenyl or cyclohexyl orheterocyclic aryl groups comprising five-to-ten-membered heteroaromaticswherein the hetero atoms are one or more of thia, aza or oxa atoms,including monocyclic heteroaryls comprising five-to-six-members havingat least one sulfur, nitrogen or oxygen atom as the heteroato m, andbicyclic heteroalkyls having up to ten members and having, as one of thecyclic moieties, a five-to-six-membered heteroaromatic ring with atleast one sulfur, nitrogen or oxygen atom, and including specificallypyridyl, piperidyl, quinolyl, imidazolyl, pyrazinyl, pyrrolyl, thien yl,furyl, thiazolyl, thiadiazolyl, pyrazolyl, oxazolyl, pyrimidinyl, andN-alkylated derivatives thereof; and R represents cyano, aminoalkyl orloweralkyl-carbonylamino-loweralkyl. Acid addition salts, such as thehydrochloride, fumarate, maleate and hexamate and loweralkyl quaternaryammonium derivatives of those substituted indoles containing a basicnitrogen in the R or R position are also included in the invention.

Compounds of the structure represented by the formula are prepared bycondensing 4,S-dimethoxy-Z-nitrophenyl acetonitrile with an aldehydeselected from the group consisting of phenyl, halophenyl,loweralkoxyphenyl, cyclohexyl, aminophenyl, loweralkylaminophenyl,di-loweralkylaminophenyl, loweralkylamino-loweralkyloxyphenyl, pyridyl,and N-loweralkyl piperidyl aldehydes in the presence of a catalyticamount of piperidine and subsequently reductively cyclizing theresulting j8-substituted-u-(4,5-dimethoxy-Z-nitrophenyl) acrylonitrile.

For the reductive cyclization of the [i-substituted-a- (4,-dimethoxy-2-nitrophenyl) acrylonitriles, a catalytic or 3,467,670Patented Sept. 16, 1969 chemical procedure that produces an intermediatestage of reduction and subsequently gives rise to cyclization to producethe corresponding indole may be employed. For example, under properconditions catalysts such as iron, nickel, zinc, and tin and acids suchas acetic, propionic, and hydrochloric may be employed. In the samemanner and under proper conditions, hydrogen and palladium may beemployed.

The reductive cyclization of the ,8 substituted oz (4, 5 dimethoxy 2nitrophenyl) acrylonitriles is desirably achieved by adding iron powderto a refluxing solution of the nitrile in a glacial acetic acid andallowing the reaction mixture to reflux for 2 to 5 hours. The solvent isdistilled under diminished pressure and the crude product is purified byrecrystallization. The elemental analyses as well as ultra violetabsorption, infrared absorption and nuclear magnetic resonance spectrasupport the assignment of the indole structures described herein.

3-N-acylamidoloweralkyl derivatives of the 3-cyano-2-substituted-5,6-dimethoxyindoles of this invention may be prepared byhydrogenating the cyanoindole in the presence of an acylating agent suchas acetic anhydride over a nickel catalyst in the presence of a basiccocatalyst. Any other suitable method for reducing the cyano group andacylating may be employed.

As used herein, pyridyl represents 2-pyridyl, 3-pyridyl or 4-pyridyl. Inthe same manner, N-loweralkylpiperidyl represents2-N-loweralkylpiperidyl, 3-N-loweralkylpiperidyl and4-N-loweralkylpiperidyl.

As used herein, loweralkyl may be straight or branch chained and havefrom 1 to 4 carbon atoms, such as, for example, methyl, ethyl, propyl,isopropyl, butyl, isobutyl, tertiary butyl and the like.

The compounds of this invention absorb ultra violet light and are usefulas sun-screening materials in salves and ointments. In addition, becauseof their solubility in organic materials generally, they may be used asultra violet absorbers in plastics and resins, such as polystyrene,polyethylene, polypropylene, polyacrylics (methacrylate resins,polyacylamides, polyacrylonitrile fibers), polyamide fibers (nylon e.g.)and polyester fibers. In the latter use, the inclusion of 0.01 to 5percent of the absorber, based on the polymer weight, is sufiicient torender protection against ultra violet light, such as in plastic film orlight filters. The absorber may be incorporated in the mixtures ofmonomers before polymerization to form the polymer or it may beincorporated in the polymer at any stage during its handling, as bymilling into the polymer together with other compounding ingredients orduring the spinning of polymers into fibers, etc.

The following examples are intended to illustrate, but not to limit, thescope of the invention.

EXAMPLE I A solution of 6.59 grams of 4,S-dimethoxy-Z-nitrophenylacetonitrile and 4.1 grams of 4-pyridine carboxaldehyde in 250 ml. ofboiling absolute alcohol is treated with 3.13 ml. of piperidine. Thesolution is boiled for 2 /2 hours and allowed to stand at roomtemperature for 2 days. A yellow precipitate is obtained. The mixture isfiltered and the precipitate collected to yielda-(4,5-dimethoxy-2-nitrophenyl) B (4-pyridyl)acrylonitrile. Meltingpoint 201 C.

EXAMPLE II A solution of 6 grams ofa-(4,S-di-methoxy-Z-nitrophenyl)-/3-(4-pyridyl)acrylonitrile in aboutml. of glacial acetic acid is heated on a steam bath with 3.38 grams ofiron powder under continuous stirring for several hours. The mixture isthen filtered. The residue from filtration is mixed with water andfiltered again. The aqueous filtrate is then made basic by the additionof potassium bicarbonate. The yellow precipitate is3-cyano-5,6-dimethoxy- 2(4-pyridyl)indole. Melting point above 310 C.

EXAMPLE III To a mixture of 3 grams of 3-cyano-5,6-dimethoxy-2(4-pyridyl)indole in approximately 150 ml. of chloroform is added 4.14grams of methyl iodide. The mixture is refluxed for about 3 hours. Thereaction is stirred overnight for about 16 hours. The mixture is thendistilled under reduced pressure to about /3 the volume and filtered toyield 4 (3-cyano-5,6-dimethoxy-2-indolyl)-1-methylpyridinium iodide.Melting point, 282-283 C.

EXAMPLE IV A 5.0 gram quantity of3-cyano-5,6-dimethoxy-2(4-pyridyl)indole is hydrogenated at roomtemperature in 200 ml. acetic anhydride containing 20 grams sodiumacetate (anhydrous) using Raney nickel as the catalyst. Removal of thecatalyst yields a filtrate which is evaporated under reduced pressure toremove most of the solvent, leaving a thick oil. The oil is treated withice water and made basic with the addition of 10 percent sodiumhydroxide solution to give a white solid. The solid is recrystallizedfrom methanol and water to give the white crystalline product3-acetamidomethyl 2 (1-acetyl-4-piperidyl)-5,6-dimethoxyindole. Meltingpoint, 157158 C.

EXAMPLE V To a refluxing solution of 22.5 grams of 4,5-dimethoxy-2-nitrophenyl acetonitrile in 400 ml. of absolute ethanol is added inportions a solution of 11 grams 3-pyridine carboxaldehyde in 50 ml. ofabsolute ethanol, and 8 ml. of piperidine. The resulting solution isallowed to reflux for 2% hours and cooled. The bright yellow product a-(4,S-dimethoxy-Z-nitrophenyl)-/3-(3 pyridyl)acrylonitrile crystallizesfrom the solution. Melting point, 204 C.

EXAMPLE VI A mixture of 5 grams ofa-(4,5-dimethoxy-2-nitrophenyl)-/8-(3-pyridyl)acrylonitri1e and 10percent palladium on carbon in a mixture of ethyl acetate and ethanol isshaken with hydrogen for 1 hour. The catalyst is filtered off and thefiltrate is distilled in vacuo to remove the solvent. The product isot-(2-amino 4,5 dimethoxyphenyl)-/i-(3-pyridyl)acrylonitrile. Meltingpoint, 130 C.

EXAMPLE VII A solution of 12 grams ofu-(4,5-dimethoxy-2-nitrophenyl)-/3-(3-pyridyl)acrylonitrile inapproximately 90 ml. of glacial acetic acid is heated on a steam bathwith 6.76 grams of iron powder under continuous stirring for severalhours. The mixture is filtered and the residue is mixed with water andfiltered again. Both the acetic acid filtrate and the aqueous filtrateare made basic by the addition of potassium bicarbonate. The productobtained is 3-cyano- 5,6-dimethoxy-2-(3-pyridyl)indole. Melting point,238- 239 C.

EXAMPLE VIII A solution of 5.5 grams of 3-cyano-5,6-dimethoxy-2-(3-pyridyl)indole and 5.5 grams of methyl iodide in 150 ml. ofdimethoxyethane is allowed to reflux for 4 hours. As the reactionproceeds, the solid product precipitates out from the solution. Thereaction mixture is cooled and filtered to give3-(3-cyano-5,6-dimethoxy-2-indolyl)-1- methylpyridinium iodide. Meltingpoint, 300301 C.

EXAMPLE IX To a solution of 10 grams ofa-(4,5-dimethoxy-2-nitrophenyl)-fl-(4-pyridyl) acrylonitrile inapproximately 275 ml. of chloroform is added 12.4 grams of methyl iodidewith continuous stirring. The reaction is refluxed for approximately 1hour and is allowed to continue stirring for approximately 21 hours. Thereaction mixture is filtered to yield a precipitate which isrecrystallized from methanol to give crystals of4-(B-cyano-4,S-dimethoxy-Z-nitrostyl ryl)-1-methylpyridinium iodide.Melting point, 216- 217 C.

EXAMPLE X A 10 gram sample of u-(4,5-dimethoxy-Z-nitrophenyl)-B-(3-pyridyl) acrylonitrile is added to 300 ml. of 1,2-dimethoxyethanecontaining 9.1 grams of methyl iodide. The reaction mixture is refluxedwith stirring for 1 hour and filtered to give an orange precipitate of3-(fi-cyano 4,5-dimethoxy-2-nitrostyryl) 1 methylpyridinium iodide whichis recrystallized from methanol to yield yellow needles. Melting point,206207 C.

U.V. absorption in methanol: 219 m (29,500); 255 m (518,200); 270 m(616,400); 297 m (e12,700).

EXAMPLE XI To a mixture of 3 grams of 4-(fi-cyano-4,5-dimethoxy-2-nitrostyryl)-l-methylpyridinium iodide in ml. of methanol is added inportions 1.1 gram of sodium borohydride and the reaction mixture isallowed to stand at room temperature for 1 hour while stirring. Duringthis period the color of the reaction mixture changes slowly from darkbrown to light brown. The methanol solution is distilled in vacuo andml. of ice water is added to the residue. The water insoluble residuea-(4,5-dimethoxy 2 nitrophenyl) B (1,2,3,6 tetrahydro 1-methyl-4-pyridyl) acrylonitrile is isolated by filtration and dried inair at room temperature. Melting point, 136 C.

EXAMPLE XII To a warm solution of 30 grams of 4,5-dimethoxy-2-nitrophenylacetonitrile in 300 ml. of ethanol, 25 grams ofp-diethylaminobenzaldehyde is added. The solution is treated with 9.45ml. of piperidine and allowed to reflux for 6 hours. The reactionmixture is cooled and filtered to yield a bright orange precipitate. Theprecipitate is recrystallized from methanol to give fluffy orange platesof a (4,5dimethoxy-Z-nitrophenyl)-fl-(4-diethylaminophenyl)acrylonitrile. Meltingpoint, 123124 C.

EXAMPLE XIII To refluxing solution of 10 grams of a-(4,5-dimethoxy 2nitrophenyl) [i (4 diethylarninophenyl)acrylonitrile in 250 ml. ofglacial acetic acid is added in portions 2.94 grams of iron powder. Theresulting reaction mixture is allowed to reflux for 2% hours and is thenfiltered. The filtrate is distilled under diminished pressure. Theresidue is treated with 150 ml. of water, filtered and the residue andfiltrate (from filtration) are treated with 100 ml. of methanol and 10percent sodium hydroxide solution. The solid product is filtered andrecrystallized from hot boiling methanol with the addition of water toyield 3 cyano-5,6-dimethoxy-2-(p-diethylaminophenyl)indole. Thehydrochloric acid addition salt is prepared by reacting 3cyano-5,6-dimethoxy-2-(p-diethylaminophenyl)indole with hydrogenchloride in ether. In a similar manner other acid addition salts such asthe fumarate, maleate and hexamate salts are prepared by using thecorresponding acid in ether solution.

EXAMPLE XIV A mixture of 6 grams of sodium acetate, 7.6 grams of 3 cyano5 ,6-dimethoxy-2-(p-diethylaminophenyl)indole and two teaspoonfuls ofnickel catalyst in 150 ml. of acetic anhydride is shaken with hydrogenat room temerature for 24 hours. After the theoretical amount ofhydrogen has been taken up, the mixture is filtered. The aceticanhydride is hydrolyzed with ice water and the acid solution ispartially neutralized with 30 grams of sodium hydroxide in 100 ml. ofwater. The white product formed is 3-acetamidomethyl-2-(p-diethylaminophenyl)- 5,6-dimethoxyindole. Melting point, 194C.

EXAMPLE XV A solution of 30 grams of 4,5-dimethoxy-2-nitrophenylacetonitrile, 23 grams of p-dimethylaminobenzaldehyde and ml. ofpiperidine in 400 ml. of methanol is allowed to reflux for 3 /2 hours.Upon cooling and filtering the mixture,a-(4,5-dimethoxy-2-nitrophenyl)-;3-(pdimethylaminophenyl)acrylonitrileis obtained. Melting point, 181 C.

EXAMPLE XVI To a refluxing solution of 16 grams of (4,5-dimethoxy 2nitrophenyl) 8 (p dimethylaminophenyl) acrylonitrile in 200 m1. ofacetic acid is added in portions 5.1 grams of iron powder and thereaction mixture is allowed to reflux for 6 hours. The reaction mixtureis filtered and the residue is washed with methanol twice to yield 3cyano 5,6 dimethoxy-Z-(p-dimethylaminophenyl)indole. Melting point,265-266 C.

EXAMPLE XVII EXAMPLE XVIII To a warm solution of 22 grams of4,5-dimethoxy-2- nitrophenylacetonitrile in 400 ml. of absolute ethanolis added 11 grams of pyridine-Z-carboxaldehyde in 50 ml. of absolutealcohol and 8 ml. of piperidine. The reaction mixture is refluxed for 2hours and is thereafter cooled and filtered to givea-(4,5-dimethoxy-2-nitrophenyl)-;3-(2- pyridyl) acrylonitrile.Recrystallization from ethyl acetate gives pure material. Melting point,187-189 C.

EXAMPLE XIX To a refluxing solution of 30 grams of 4,5-dimethoxy-Z-nitrophenylacetonitrile in 250 ml. of absolute methanol is added 33grams of p-2-diethylaminoethoxybenzaldehyde and 10 ml. of piperidine.The resulting mixture is refluxed for 6 hours, cooled, filtered to yielda solid which is recrystallized from methanol to obtainfi-[p-(Z-diethylaminoethoxy) phenyl] a (4,5-dimethoxy-2-nitrophenyl)acrylonitrile. Melting point, 105 C.

U.V. absorption in methanol: 230 m (e18,800); 311 m (628,700)- EXAMPLEXX To a refluxing solution of 20.5 grams of 18-[p-(2-diethylaminoethoxy)phenyl] on (4,5 dimethoxy-2-nitrophenyl)acrylonitrile in 200 ml. ofacetic acid is added in portions, 5.6 grams of iron powder. The reactionmixture is refluxed for 4 hours. The mixture is filtered and thefiltrate is distilled in vacuo. The residue is treated with 20.0 ml. ofwater and 30 percent sodium hydroxide to make the solution basic, andfiltered. The product obtained is 3-cyano-2-[p-(2-diethylaminoethoxy)phenyl]- 5,6-dimethoxyindole which is recrystallized several times fromdilute methanol. Melting point, 165 C.

EXAMPLE XXI A solution of grams of4,5-dimethoxy-2-nitrophenylacetonitrile and 15 grams ofpyrrole-Z-carboxyaldehyde in about 250 ml. of absolute ethanol istreated with 7.23 ml. of piperidine under refluxing. The refluxing iscontinued for 1 hour. The mixture is filtered to yield a solid which isrecrystallized from methanol-ethanol to give lit-(4,5-dimethoxy-Z-nitrophenyl -fi (2-pyrrolyl) acrylonitrile, red crystals.Melting point, 193-194 C.

U.V. absorption in methanol: 218 m (616,600); 247 m (611,100); 337 m(624,400).

6 EXAMPLE XXII A solution of 15 grams of 4,5-dimethoxy-2-nitropheny1-acetonitrile and 9.5 grams of N-methylpyrrole-Z-carboxaldehyde in about250 ml. of absolute ethanol is treated with 7.23 ml. of piperidine andrefluxed for approximately 4 hours. The mixture is filtered to yield anorange precipitate 'of a-(2-I1itI'O-4,5 -dimethoxyphenyl) B (l-methyl-2-pyrrolyl) acrylonitrile. Melting point, 182-183 C.

EXAMPLE XXIII A solution of 4.68 grams of4,S-dimethoxy-Z-nitrophenylacetonitrile and 3.04 grams of2thiophenecarboxaldehyde in approximately 79 ml. of absolute ethanol istreated with 2.25 ml. of piperidine and refluxed about 1 hour. Thereaction is cooled and filtered to give a solid which is crystallizedfrom methanol to give a-(4,5-dimethoxy-2- nitrophenyl)-fi-(2-thienyl)acrylonitrile. Melting point, 187188 C.

EXAMPLE XXIV To a hot solution of 20 grams of u-(4,5-dimethoxy-2-nitrophenyl)-fi-(2-thienyl) acrylonitrile in ml. of glacial acetic acid,7.06 grams of iron powder is added. The mixture is stirred under refluxfor 2 hours and 15 minutes. The reaction mixture is then filtered toyield a solid which is recrystallized from methanol to give silverywhite needles of 3-cyano-5,6-dimethoxy-2-(Z-thienyl) indole. Meltingpoint, 209-210 C.

EXAMPLE XXV To a warm solution of 30 grams of 4,5-dimethoxy-2nitrophenylacetonitrile in 300 ml. of absolute ethanol, 15 grams offurfural and 9.45 grams of piperidine (catalyst) are added. The reactionsolution is refluxed for 1 /2 hours, cooled and filtered to yielda-(2-nitro-4,5-dimethoxyphenyl)-fl-(2-furyl) acrylonitrile. Meltingpoint, 18l182 C U.V. absorption in methanol: 213 m (12,200); 244 mp.(12,900); 316 m (625,600).

EXAMPLE XXVI A solution of 17.7 grams ofa-(2-nitro-4,5-dimethoxyphenyl)-fl-(2-furyl) acrylonitrile in 300 ml. ofglacial acetic acid is stirred with 6.57 grams of iron powder underrefluxing for about 2 /2 hours. The reaction is allowed to cool and isfiltered. Evaporation of the filtrate leaves a gum which crystallizesupon treatment with water. Recrystallization of the solid from aqueousethanol gives 3- cyano-2-(2-furyl) 5,6 dimethoxyindole. Melting point,180181 C. U.V. absorption in methanol: 237 mu (e19,100); 336 m(629,400).

EXAMPLE XXVII To a refluxing solution of 10 grams of 4,5-dimethoxy-2-nitrophenylacetonitrile in 200' m1. of methanol is added in portions 7grams of cyclohexanecarboxyaldehyde and 3 ml. of piperidine. The mixtureis allowed to reflux for 6 hours. The reaction mixture is cooled and thesolid product precipitated is filtered and crystallized from methanol togive B-cyclohexyl-u- (4,S-dimethoxy-Z-nitrophenyl) acrylonitrile.Melting point, 161 C.

U.V. absorption in methanol: 248 m (612,400); 295, 342 mu.

EXAMPLE XXVIII To a refluxing solution of 22.5 grams offi-cyclohexyla-(4,5-dimethoxy-2-nitrophenyl)acrylonitrile in 200 ml. ofacetic acid is added in portions 8.4 grams of iron powder. The resultingmixture is refluxed for 6 'hours. The reaction mixture is filtered andthe filtrate is evaporated under diminished pressure to give a residuewhich is recrystallized from ethyl acetate-hexane to obtain 3-cyano-2-cyclohexyl-S,6-dimethoxyindole. Melting point, 137l39 C.

7 EXAMPLE XXIX To a warm solution of 30 grams of 4,5-dimethoxy-2-nitrophenylacetonitrile in 300 ml. of absolute ethanol, 20 grams of4-cyanobenzaldehyde and 9.45 ml. of piperidine are added. The reactionsolution is refluxed for 3 hours. The reaction mixture is filtered toyield a bright yellow product which is crystallized from methanol togive nt- (2-nitro-4,S-dimethoxyphenyl 3- (4cyanophenyl) aciylonitrile.Melting point, 214215 C.

U.V. absorption in methanol: 246 m (614,200); 289 m (626,600)- EMMPLEXXX A solution of 5 grams ofa-(2-nitro-4,5-dimethoxyphenyl)-B-(4-cyanophenyl)acrylonitrile in 175ml. of acetic acid is stirred with 1.66 grams of iron powder underrefluxing conditions for approximately 2 hours. The reaction mixture iscooled and filtered. The solid product is recrystallized from methanolto yield 3-cyano-5,6-dimethoxy-2-(4-cyanophenyl)indole. Melting point,283 C.

U.V. absorption in methanol: 219 m (628,000); 242 m (516,300); 359 m,(619,90

EXAMPLE XXXI To a refluxing solution of 21 grams of 4,5dimethoxy-2-nitrophenylacetonitrile in 200 ml. of methanol is added in portions, 14grams of p-chlorobenzaldehyde in 100 ml. of methanol and ml. ofpiperidine. The mixture is refluxed for 4 hours. The reaction mixture iscooled and the solid product is filtered and recrystallized frommethanol to give [3-(p-chlorophenyl)-a-(4,5-dimethoxy 2 nitro phenyl)acrylonitrile. Melting point, l76.5-l77 C.

U.V. absorption in methanol: 295 Ill 1. (25,800); 223 m (618,700).

EXAMPLE XXXII To a refluxing solution of 24 grams of fl-(p-chlorophenyl)x- 4,5 -dimethoxy-2-nitrophenyl) acrylonitrile in 200 ml. of glacialacetic acid is added in portions 8 grams of iron powder. The reactionmixture is refluxed for 3 to 4 hours, cooled and then filtered. Theresidue is washed with hot methanol and boiling Water and crystallizedfrom methanol to give 3-cyano-2-(p-chlorophenyl)-5,6-dimethoxyindole.Melting point, 284285 C.

U.V. absorption in methanol: 331 mu (e22,000); 236 mp. (624,800).

EXAMPLE XXXIII A 3 gram quantity of3-cyano-2-(p-chlorophenyl)-5,6-dimethoxyindole is treated with 75 ml. ofacetic anhydride. Upon heating the sample gradually goes into solution.The reaction is refluxed for about 2 hours and allowed to cool to roomtemperature. The precipitated material, 1-acety1-3-cyano-2-(p-chl0rophenyD-5,6-dimethoxyindole is recrystallized frombenzene. Melting point, 266267 C.

U.V. absorption in methanol: 218 m (610,800); 244 mp (610,000); 327 mu(611,600).

EXAMPLE XXXIV A mixture of 3 teaspoons of Raney nickel catalyst,(previously washed with acetic anhydride), 10 grams of anhydrous sodiumacetate, 5 grams of 2-(p-chlorophenyl)-3-cyano-5,6-dimethoxy-l-indolepropionitrile in 200 ml. of aceticanhydride, is shaken with hydrogen at room temperature for 4 hours. Thereaction mixture is filtered to yield a dark filtrate which isevaporated under reduced pressure to yield a gum. Upon standing over theweekend, the gum crystallizes to a greenish precipitate. Ice is addedand the mixture is filtered to yield a precipitate of3-acetamidomethyl-1-acetamidopropyl-2-(p-chlorophenyl) 5,6-dimethoxyindole. The material is recrystallized from aqueous methanol toyield yellow crystals. Melting point, 224- 225 C.

8 EXAMPLE XXXV A 15.0 gram quantity of 3-cyano-2-(p-chlorophenyl-5,6-dimethoxy-indole is dissolved in 380 ll'l'll. of dimethylformamide andfiltered. The filtrate is then treated with 180 ml. of acrylonitrile and6 ml. of 40 percent alcoholic benzyltrimethylammonium methoxide to whicha few drops of water have been added. The solution is then heated on asteam bath for 3 hours and is then refrigerated for 2 days. The reactionmixture is filtered and washed with water. Recrystallization fromdimethylformamide gives 2-(pchlorophenyl)-3-cyano-5,6-dimethoxy 1indolepropionitrile. Melting point, 262264 C.

EXAMPLE XXXVI A 6.66 gram quantity of 3-cyano-5,6-dimethoxy-2-(4-cyanophenyDindole is refluxed for 29 /2 hours in a solution of 3.52grams of sodium hydroxide in 50 ml. of water. To this is added 20 m1. ofpercent ethanol. The reaction mixture is allowed to stand at roomtemperature for 62 hours. The reaction mixture is cooled and filtered toyield a solid, which is recrystallized from water to give sodium p (3cyano 5,6 dimethoxyindol-Z-yl)benzoate. Melting point, above 340 C.Acidification with dilute aqueous hydrochloric acid yieldsp-(3-cyano-5,6-dimethoxyindol 2 yl)benzoic acid. Melting point, above340 C.

EXAMPLE X)Q(VII Using the procedure of Example XXXI and replacing thep-chlorobenzaldehyde with an equivalent amount of benzaldehyde, theproduct recovered isfi-phenyl-.a-(4,5-dimethoxyl-Z-nitrophenyl)acrylonitri1e.

EXAMPLE XXXVIII Using the procedure of Example XXXII and replacing the13 (p chlorophenyl)-a-(4,5-dimethoxy-2-nitrophenyl) acrylonitrile withan equivalent amount of the ,B-phenyl-u- (4,5-dimethoxy-Z-nitrophenyl)acrylonitrile, the product recovered is3-cyano-2-phenyl-5,6-dimethoxyindole. Melting point, 254255 C.

U.V. absorption in methanol: 225 m (627,800); 330 m (628,800).

EXAMPLE XXXIX Using the procedure of Example XXXI and replacing thep-chlorobenzaldehyde with an equivalent amount ofp-me'thoxybenzaldehyde, the product recovered is fi-(pmethoxyphenyl) a(4,S-dimethoxy-Z-nitrophenyl)acrylonitrile. Melting point, 200-201 C.yellow plates.

U.V. absorption in methanol: 237 III/l. (616,700); 319 mp. (624,000).

EXAMPLE XL Using the procedure of Example XXXII and replacing thefi-(p-chlorophenyl) a (4,5-dimethoxy-2-nitrophenyl) acrylonitrile withan equivalent amount ofB-(p-methoxyphenyl)-ix-(4,S-dimethoxy-Z-nitrophenyl)acrylonitrile, theproduct recovered is 3-cyano-2-(p-methoxyphenyD-S,6-dimethoxyindole.Melting point, 247-248" C. pink plates.

U.V. absorption in methanol: 238 mp. (622,800); 332 mp 627,600).

EXAMPLE XLI Using the procedure of Example XXXI and replacing thep-chlorobenzaldehyde with an equivalent amount of p-aminobenzaldehyde,the product recovered is fi-(paminophenyl) a (4,5dimethoxy-2-nitrophenyl)acrylonitrile.

EXAMPLE XLII Using the procedure of Example XXXII and replacing the J3(p chlorophenyD-a-(4,5-dilmethoxy-2-nitrophenyl) acrylonitrile with anequivalent amount offl-(p-aminophenyl)-a-(4,5-dimethoxy-2-nitrophenyl)acrylonitrile, theproduct recovered is 3-cyano-2-(p-aminophenyl)-5,6-dimethoxyindole.

9 EXAMPLE XLIII Using the procedure of Example XXXI and replacing thep-chlorobenzaldehyde with an equivalent amount ofpmethylarninobenzaldehyde, the product recovered isfl-(pmethylaminophenyl) a (4,5 dimethoxy-Z-nitrophenyl) acrylonitrile.

EXAMPLE XLIV Using the procedure of Example XXXII and replacing the p (pchlorophenyD-a-(4,S-dimethoxy-Z-nitrophenyl) acrylonitrile with anequivalent amount of B-(p-me'thylaminophenyl) a (4,5dimethoxy-Z-nitrophenyl)acrylonitrile, the product recovered is3-cyano-2-(p-methylaminophenyl)-5,6-dimethoxyindole.

EXAMPLE XLV Using the procedure of Example XXXI and replacing thep-chlorobenzaldehyde with an equivalent amount ofp-trifluoromethylbenzaldehyde, the product recovered is p-(p-trifluoromethylphenyD-a-(4,5-dimethoxy-2-nitropheny1) acrylonitrile.

EXAMPLE XLVI 10 I claim: 1. A member of the group consisting of5,6-dimethoxywherein R is a member of the group consisting ofloweralkylcarbonylamino-loweralkyl; R is a member of the groupconsisting of chlorophenyl and di-loweralkylaminophenyl and R is amember of the group consisting of loweralkylcarbonyl-aminoloweralkyl.

2. 3 acetamidomethyl 2 (p diethylaminopheny1)- 5,6-dimethoxyindole.

3. 3 acetamidomethyl 2 (p dimethylaminophenyD- 5,6-dimeth0xyindole.

4. 3 acetamidomethyl 1 acetamidopropyl 2 (pchlorophenyl-5,6-dimethoxyindole.

References Cited UNITED STATES PATENTS 3,104,241 9/1963 Enenkel et a1260247.2

ALEX MAZEL, Primary Examiner I. A. NARCAVAGE, Assistant Examiner

